Flashcards in Lecture 2/3 - Pharmacokinetics Deck (92):
What are the two methods of passive transport?
Channel mediated + Transporter mediated
What are three major components that go with carrier mediated transport?
What are the two methods of carrier mediated methods?
Facilitated diffusion + Active transport
What is different about active transport compared to facilitated diffusion?
This method needs ATP in order to function
What is transcytosis?
Drug molecules + fluids are engulfed by the cell membrane and transported within the cell
What is the pH of most drugs given?
Weak acids or Weak bases
What is the most basic process that drugs undergo within the body ? (Hint: decides whether they are absorbed or not)
Ionization - phH dependent
What is the purpose of the Henderson-Hasselbach equation?
Tells you to what extent the drug is ionized within the body
What is A- form of the acid?
What is the HA form of the acid?
What is the B form of a base?
What is the BH+ form of a base?
What occurs to a weak acid within an acidic medium?
More lipid soluble
What occurs with a weak basic drug within basic medium?
What is an example, given in lecture, of an area with low pH?
The stomach (~2)
What is an example, given in lecture, of an area in the body with basic tendencies?
What occurs when a basic drug is within an acid medium? What is this called?
Ionized and therefore will accumulate within the area. Known as ion trapping
What is the rule of thumb with both strong acids and bases within the body?
Always will be ionized within the body, so they are not lipid soluble meaning they will not undergo passive diffusion
What is the basic understanding of ion trapping?
Acids will be stuck in basic environments
Bases will be stuck in acidic environments
How do you make urine more acidic?
How do you make urine more basic?
What happens when you make urine more acidic?
Increase the elimination of bases via ion trapping
What happens when you make the urine more basic?
Increased elimination of acids, via ion trapping
What are the three types of active transport?
Uniport + Symport + Antiport
What is an example of a uniport given in lecture?
What is an example of a symport given in lecture?
What is an example of an antiport given in the lecture?
What is P-gp?
What are two other names for P-gp?
-- or --
What is the function of P-gp?
Utilizes ATP to pump out a WIDE variety of drugs across both extra/intracellular membranes
Where is P-gp located?
Pretty much everywhere, important to know it is found in the BBB
What is absorption in regards to a drug?
Process where drug gains entry into body fluids (normally blood) and moves throughout the organism
What are seven things that tend to affect absorption?
Solubilty + Dissolution + Concentration + Blood flow + SA + pH + Contact time
What is bioavailability?
Amount of active drug available at the site of action
What four things play a role in bioavailability?
Decomposition of drug in intestines
Degree of absorption
Metabolism in wall of gut or liver
Transport of drug back into lumen via P-gp
What is the first pass effect?
Initial metabolism of drug, occurs through wall of gut or liver
What is the most common method by which a drug is administered?
Per os (by mouth)
What is the downside to a slow release formulation?
Absorption is irregular and erratic
What are the disadvantages to per os method of drug administration?
Destruction of drug due to low pH
Gastric emptying time
binding to food
Metabolism by microbes
Exposed to liver
What does the process of drug distribution entail?
Movement of drug from systemic circulation to organs/tissues
Where are the three popular sites in the body that drugs accumulate?
Fat + Tissues + Bone
What affects do storage depots have on the drugs metabolism?
decrease plasma levels
-- and --
prolong half lives
Where are the five sites of exclusion?
CSF + Ocular + Endolymph + Fetal + Pleural
What two components help define volume of distribution?
Plasma concentration of drug at time zero
What is the standard plasma size of a 70kg dog?
What is the standard EC compartment size in a 70kg dog?
What is the standard Total body water compartment in a 70kg dog?
What does a large Vd mean?
The drug is either distributed extensively or has bound extensively to peripheral tissues
What does a very low Vd mean?
Drug is mostly present in the plasma, very high plasma protein binding
What are the characteristics of most active drugs?
Unionized at physiological pH
Strongly bound to plasma proteins
Not readily excreted by kidneys
Remain in body for long periods of time
What is the most basic thing that happens in phase II reactions?
What is the most basic way to describe what occurs in a phase I reaction?
Modification of the molecule
What commonly occurs within the phase I reaction?
Lipid soluble parent compound converted to more polar metabolites
Most commonly these are inactive and therefore excreted
What does the phase I reaction do to the chemical structure of most drugs?
introduce or unmask functional groups (-OH, SH, NH2, etc)
What are the two types of phase I reactions?
Non-microsomal + Microsomal
Is phase I specific to certain compounds?
No, enzymes are focused on specific groups/bonds
What are five enzymes that are examples of nonmicrosomal metabolism in phase I?
What is a Phase I microsomal reaction?
Drug oxidation via P450 (and other biological variations)
How do microsomal reactions differ from non-microsomal Phase I reactions?
Induction + Inhibition can occur
How is Phase II reactions similar to Phase I?
Not compound specific
What type of reactions are Phase II reactions?
What are the results of Phase II reactions?
Larger molecular weight
Decreased biological activity
What is the only microsomal Phase II reaction?
Glucuronidation (therefore it is inducible)
What are the five major types of phase II reactions?
What is the endogenous reactant in glucuronidation?
UDP glucuronic acid
What is the transferase/location for glucuronidation?
What is the endogenous reactant for acetylation?
What is the transferase/location for Actylation?
What is the endogenous reactant for glutathione conjugation?
What is the transferase/location for glutathione conjugation?
Cytosol - Microsomes
What is the endogenous reactant for glycine conjugation?
What is the transferase/location for glycine conjugation?
What is the endogenous reactant for sulfation?
What is the transferase/location for sulfation?
What is the path for renal excretion of drugs and their metabolites?
Active tubular secretion or reabsorption
Passive diffusion across tubular epithelium
What does clearance pertain to?
The ability of the body to remove the drug
What two things does clearance relate?
Rate of drug elimination + Plasma concentration
What are the two phases of the two-compartment model?
Distribution + Elimination
Why do you see initial rapid changes in the two compartment model graph?
Shows the time it takes for the drug to reach an equilibrium between the central compartment and the plasma space
What order is the elimination phase in the two compartment model?
First-order, we know this because of it's linear pattern
What is used to get the elimination rate in the two compartment model?
K - aka the slope of the linear portion of the graph
What on the graph of the two compartment model tells you Co? What does that mean?
Where the linear line intercepts the Y-axis, this gives you the plasma concentration of the drug at time zero.
What is the most common order of elimination?
What does first order elimination mean?
constant proportion of the drug is eliminated per unit time
Why do you get first order elimination?
Elimination system is not saturated by the drug
What does half life mean?
Time required to change amount of drug in body by one-half
What are you assuming when you determine 1/2 life?
Body is single compartment
Size = Vd
Drug is distributed equally
Drug in plasma is in equillibrium w/ total volume
What is zero order elimination?
The elimination system becomes saturated after a high dose of the drug, meaning only a constant amount can be eliminated per unit time
What needs to be done to reach steady state with repeated administration?
Interval of time it takes to reach SS is equal to five half lives
What is a loading dose?
Done for immediate therapeutic concentration
What follows a loading dose?